Methods of preventing platelet alloimmunization and alloimmune platelet refractoriness and induction of tolerance in transfused recipients

Abstract

Methods and compositions for the prevention or reduction of platelet transfusion associated complications are provided. The subject methods include modifying donor whole blood or platelets prior to transfusion to prevent or reduce alloimmune platelet refractoriness.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. patent application Ser. No. 15 / 167,923 filed May 27, 2016, which is a continuation-in-part of U.S. patent application Ser. No. 14 / 886,815 filed Oct. 19, 2015, and U.S. Patent Application No. 62 / 342,831 filed May 27, 2016, both of which are hereby incorporated by reference in their entirety.STATEMENT OF GOVERNMENT SUPPORT[0002]This invention was made with United States Government support under U.S. Army Medical Research and Materiel Command Grant No. 07328001, W81XWH-07-1-0578 and Department of Defense, and in part, by a grant provided by Terumo BCT, Lakewood, Colo. The United States Government has certain rights in this invention.FIELD[0003]This invention is directed to methods of preventing transfusion related complications in recipients of donor blood or components thereof.INTRODUCTION[0004]Blood transfusion is the process of receiving blood products into one's circulation intravenously. Trans...

AI Technical Summary

Benefits of technology

[0091]This example provides methods of modifying a donor dog's platelets prior to transfusion in a dog platelet transfusion model that would prevent alloimmune platelet refractoriness. In some aspects, methods of preventing platelet alloimmunization in a dog model could be successfully transferred to patients. Specifically, in some aspects, UV-B irradiation that was 45% successful in preventing alloimmunization in the dog was 81% successful in patients in the largest prevention of platelet alloimmunization trial ever conducted in patients (TRAP Trial). (See Slichter S J, Deeg H J, Kennedy M S. Prevention of platelet alloimmunization in dogs with systemic cyclosporine and by UV-irradiation or cyclosporine-loading of donor platelets. Blood 1987; 69(2):414-418; The Trial To Reduce Alloimmunization To Platelets Study Group. Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. N Engl J Med 1997; 337:1861-1869.) The fact that UV-B irradiation was even more successful in patients than in the dog is probably because the dogs had a normal immune system while being transfused versus a compromised immune system in the study patients who were receiving induction chemotherapy for acute myelogenous leukemia (AML). Therefore, any beneficial approach in the dog is likely to be even more successful in cancer patients receiving chemotherapy or stem cell transplants. These patients, who often receive prolonged platelet therapy, would benefit the most from methods to prevent alloimmunization.

[0092]Studies in a dog model have been performed suggesting that just a quantitative reduction in the number of residual white blood cells (WBCs) was not sufficient to prevent alloimmunization. Transfused WBCs contain antigen presenting cells (APCs) that present donor antigens to the recipient's immune system leading to alloimmunization. In fact, different methods of leukoreduction using centrifugation (C-LR) versus filtration (F-LR) that both pr

Problems solved by technology

Transfusions of blood products is associated with complications, including immunologic transfusion reactions.

Alloimmunization can result in the rejection of transfused or transplanted tissues, such as platelets, which leads to platelet refractoriness.

This pro

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